Identifying Plasma Biomarkers with high specificity for major depressive disorder: A multi-level proteomics study

Area of Science:

• Neuroscience
• Biochemistry
• Genomics

Background:

• Major depressive disorder (MDD) lacks objective diagnostic biomarkers due to its complex biology.
• Developing specific blood-based biomarkers would greatly aid MDD diagnosis.

Purpose of the Study:

• To identify and validate plasma protein biomarkers for the objective diagnosis of major depressive disorder (MDD).
• To assess the diagnostic potential of identified proteins and a protein panel in distinguishing MDD from other psychiatric conditions.

Main Methods:

• Plasma proteomic analysis was performed on drug-naïve MDD patients and healthy controls.
• Bioinformatics and machine learning were used to screen candidate proteins.
• Candidate biomarkers were validated in independent cohorts, including patients with schizophrenia (SZ) and bipolar I disorder (BD-I), and in postmortem brain tissue.

Main Results:

• Levels of C-reactive protein (CRP), antithrombin III (ATIII), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), and vitamin D-binding protein (VDB) were elevated in MDD patients.
• ITIH4 and VDB showed significantly higher levels specifically in MDD compared to SZ and BD-I patients.
• Increased VDB and ITIH4 were found in both plasma and brain tissue of MDD patients.
• A four-protein panel demonstrated high accuracy in distinguishing MDD from healthy controls and other disorders.

Conclusions:

• Plasma ITIH4 and VDB show potential as specific biomarkers for MDD.
• The identified four-protein panel is a promising candidate for a clinical diagnostic marker for MDD.